Identification
NameEnoximone
Accession NumberDB04880
TypeSmall Molecule
GroupsApproved, Investigational
Description

Enoximone is a selective phosphodiesterase inhibitor with vasodilating and positive inotropic activity that does not cause changes in myocardial oxygen consumption. It is used in patients with congestive heart failure. Trials were halted in the U.S., but the drug is used in various countries.

Structure
Thumb
Synonyms
Perfan
External IDs MDL 17,043 / MDL-17043
Product Ingredients Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
PerfanNot Available
Brand mixturesNot Available
Categories
UNIIC7Z4ITI7L7
CAS number77671-31-9
WeightAverage: 248.301
Monoisotopic: 248.061948328
Chemical FormulaC12H12N2O2S
InChI KeyZJKNESGOIKRXQY-UHFFFAOYSA-N
InChI
InChI=1S/C12H12N2O2S/c1-7-10(14-12(16)13-7)11(15)8-3-5-9(17-2)6-4-8/h3-6H,1-2H3,(H2,13,14,16)
IUPAC Name
4-methyl-5-[4-(methylsulfanyl)benzoyl]-2,3-dihydro-1H-imidazol-2-one
SMILES
CSC1=CC=C(C=C1)C(=O)C1=C(C)NC(=O)N1
Pharmacology
Indication

For the treatment of congestive heart failure.

Structured Indications Not Available
Pharmacodynamics

Enoximone is a phosphodiesterase inhibitor (type III) that increases the force of contraction of the heart and dilates blood vessels. In June 2005, Myogen announced that they were discontinuing development of enoximone due to negative results. The drug is approved for use in the UK.

Mechanism of action

Further research is required to determine accurately the mechanism of action of drugs with phosphodiesterase inhibitory activity, however, inhibition of PDE3 inhibits degredation of cGMP. This allows for increased NO release and vascular relaxation.

TargetKindPharmacological actionActionsOrganismUniProt ID
cGMP-inhibited 3',5'-cyclic phosphodiesterase AProteinyes
inhibitor
HumanQ14432 details
Related Articles
Absorption

Bioavailabvility is 50% following oral administration.

Volume of distributionNot Available
Protein binding

85%

Metabolism

Hepatic oxidation

Route of eliminationNot Available
Half life

4-10 hours

ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions Not Available
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Sandroni C, Cavallaro F, Caricato A, Scapigliati A, Fenici P, Antonelli M: Enoximone in cardiac arrest caused by propranolol: two case reports. Acta Anaesthesiol Scand. 2006 Jul;50(6):759-61. [PubMed:16987374 ]
  2. van der Maaten JM, de Vries AJ, Rietman GW, Gallandat Huet RC, De Hert SG: Effects of preemptive enoximone on left ventricular diastolic function after valve replacement for aortic stenosis. J Cardiothorac Vasc Anesth. 2007 Jun;21(3):357-66. Epub 2006 May 4. [PubMed:17544886 ]
  3. Schauvliege S, Van den Eede A, Duchateau L, Gasthuys F: Cardiovascular effects of enoximone in isoflurane anaesthetized ponies. Vet Anaesth Analg. 2007 Nov;34(6):416-30. Epub 2007 Aug 13. [PubMed:17696974 ]
  4. Boldt J, Suttner S: Combined use of ultra-short acting beta-blocker esmolol and intravenous phosphodiesterase 3 inhibitor enoximone. Expert Opin Pharmacother. 2007 Sep;8(13):2135-47. [PubMed:17714066 ]
External Links
ATC CodesC01CE03 — Enoximone
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
3TerminatedTreatmentCongestive Heart Failure (CHF)2
4Unknown StatusTreatmentMicrocirculation / Severe Sepsis1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point (°C)256 dec °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.0682 mg/mLALOGPS
logP1.97ALOGPS
logP1.84ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)9.68ChemAxon
pKa (Strongest Basic)-7.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area58.2 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity70.05 m3·mol-1ChemAxon
Polarizability25.67 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9659
Blood Brain Barrier+0.77
Caco-2 permeable-0.5178
P-glycoprotein substrateNon-substrate0.6512
P-glycoprotein inhibitor INon-inhibitor0.9333
P-glycoprotein inhibitor IINon-inhibitor0.992
Renal organic cation transporterNon-inhibitor0.892
CYP450 2C9 substrateNon-substrate0.6586
CYP450 2D6 substrateNon-substrate0.7445
CYP450 3A4 substrateNon-substrate0.6998
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9431
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorInhibitor0.5842
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8173
Ames testNon AMES toxic0.7916
CarcinogenicityNon-carcinogens0.9418
BiodegradationNot ready biodegradable0.9737
Rat acute toxicity2.0807 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9554
hERG inhibition (predictor II)Non-inhibitor0.8438
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-004i-3910100000-ff2ed6a9d4b5b2530185View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as aryl-phenylketones. These are aromatic compounds containing a ketone substituted by one aryl group, and a phenyl group.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganic oxygen compounds
Sub ClassOrganooxygen compounds
Direct ParentAryl-phenylketones
Alternative ParentsThiophenol ethers / Benzoyl derivatives / Carbonylimidazoles / Alkylarylthioethers / Vinylogous amides / Heteroaromatic compounds / Ureas / Sulfenyl compounds / Azacyclic compounds / Organopnictogen compounds
SubstituentsAryl-phenylketone / Aryl thioether / Benzoyl / Thiophenol ether / Imidazole-4-carbonyl group / Alkylarylthioether / Monocyclic benzene moiety / Benzenoid / Azole / Heteroaromatic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Metal ion binding
Specific Function:
Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.
Gene Name:
PDE3A
Uniprot ID:
Q14432
Uniprot Name:
cGMP-inhibited 3',5'-cyclic phosphodiesterase A
Molecular Weight:
124978.06 Da
References
  1. Boldt J, Suttner S: Combined use of ultra-short acting beta-blocker esmolol and intravenous phosphodiesterase 3 inhibitor enoximone. Expert Opin Pharmacother. 2007 Sep;8(13):2135-47. [PubMed:17714066 ]
  2. Sandroni C, Cavallaro F, Caricato A, Scapigliati A, Fenici P, Antonelli M: Enoximone in cardiac arrest caused by propranolol: two case reports. Acta Anaesthesiol Scand. 2006 Jul;50(6):759-61. [PubMed:16987374 ]
Drug created on October 20, 2007 13:43 / Updated on June 24, 2017 13:23